设计随机对照试验,估算多癌检测筛查可降低的癌症死亡率。

IF 9.9 1区 医学 Q1 ONCOLOGY JNCI Journal of the National Cancer Institute Pub Date : 2024-10-09 DOI:10.1093/jnci/djae247
Ping Hu, Philip C Prorok, Hormuzd A Katki
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引用次数: 0

摘要

背景:要确定使用多癌检测(MCD)筛查是否能挽救生命,需要进行随机对照试验(RCT)。为了给随机对照试验的设计提供信息,我们估算了假设的多癌症检测随机对照试验的癌症死亡率结果:我们使用之前用于规划 NLST 的 Hu-Zelen 模型,针对不同的 RCT 设计参数和 MCD 检测参数,估算了 9 种癌症的死亡率降低率、样本大小和功率:我们的基础案例 RCT 每年筛查 5 次,每组筛查 10 万名 60-74 岁的人,这些人也接受标准护理筛查,在 7-9 年的时间里,87%-89% 的功率可检测到 9-10% 的死亡率降低(NNS = 578-724)。大多数被预防的死亡病例来自肺癌(基本情况(64-66%)和所有敏感性分析),8-10%来自结直肠癌,26%来自其他 7 种癌症,其中大多数来自胃/卵巢/食道癌(由于 1 期存活率极高),较少来自肝/胰腺癌(1 期存活率较低)或头颈部癌症/淋巴瘤(4 期存活率极高)。大多数癌症部位的死亡率降低幅度有限。基础研究结果对临床前状态下的测试灵敏度、分期转移和平均停留时间(尤其是肺癌)很敏感,但通过招募风险更高的人群,可以恢复 90% 的功率:结论:大规模 MCD RCT 具有 89% 的功率,可以检测到从试验开始到 7-9 年的较短时间内癌症死亡率降低 10%。与乳房 X 线照相筛查相比,MCD RCT 的估计 NNS 更为有利。在一项有效的 MCD RCT 中,大多数被预防的癌症死亡病例可能是肺癌。非肺癌/CRC 癌症部位可能在所预防的癌症死亡人数中占相当大的比例,但没有足够的力量将非肺癌死亡率的降低分离出来。
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Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening.

Background: Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs.

Methods: We used the Hu-Zelen model, previously used to plan the NLST, to estimate mortality reductions, sample-size, and power for 9 cancers for different RCT design parameters and MCD test parameters.

Results: Our base-case RCT with 5 yearly screens and 100,000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87-89% power to detect an 9-10% mortality reduction (NNS = 578-724) over 7-9 years. The majority of prevented deaths were from lung-cancers (base-case (64-66%) and all sensitivity analyses), 8-10% from colorectal-cancer, and 26% from the other 7-cancers, mostly from stomach/ovary/esophagus (due to excellent stage-1 survival) and less from liver/pancreas (poor stage-1 survival) or head/neck-cancer/lymphoma (excellent stage-4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage-shifts, and mean sojourn times in the preclinical state (especially for lung-cancer), but 90% power could be recovered by recruiting a substantially higher risk population.

Conclusions: Large-scale MCD RCTs would have 89% power to detect a ∼10% cancer-mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably to mammographic screening. Most prevented cancer-deaths in a well-powered MCD RCT would likely be from lung-cancer. Non-lung/CRC cancer sites could be a meaningful proportion of prevented cancer-deaths but power is insufficient to isolate non-lung-cancer mortality reductions.

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来源期刊
CiteScore
17.00
自引率
2.90%
发文量
203
审稿时长
4-8 weeks
期刊介绍: The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
期刊最新文献
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